Lynch Syndrome Biopathology and Treatment: The Potential Role of microRNAs in Clinical Practice

SIMPLE SUMMARY: Lynch syndrome is an autosomal dominant hereditary disease that confers a high risk of developing various types of tumors, especially colorectal and endometrial cancer. In recent years, the molecular mechanisms underlying Lynch syndrome have generated considerable interest. Several studies have highlighted the epiphenomenon of microsatellite instability, caused by a deficit in the ability of cells to repair DNA damage, as a disease-specific feature. The discovery of microRNAs has served to clarify how these small oligonucleotide molecules may contribute to the progression of Lynch syndrome by modulating the expression of several players involved in DNA repair pathways. The purpose of this review is to analyze the management of patients with Lynch syndrome by emphasizing the importance of microRNAs as markers or therapeutics for the development of novel clinical approaches. ABSTRACT: Lynch syndrome (LS), also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is an autosomal dominant cancer syndrome which causes about 2–3% of cases of colorectal carcinoma. The development of LS is due to the genetic and epigenetic inactivation of genes involved in the DNA mismatch repair (MMR) system, causing an epiphenomenon known as microsatellite instability (MSI). Despite the fact that the genetics of the vast majority of MSI-positive (MSI(+)) cancers can be explained, the etiology of this specific subset is still poorly understood. As a possible new mechanism, it has been recently demonstrated that the overexpression of certain microRNAs (miRNAs, miRs), such as miR-155, miR-21, miR-137, can induce MSI or modulate the expression of the genes involved in LS pathogenesis. MiRNAs are small RNA molecules that regulate gene expression at the post-transcriptional level by playing a critical role in the modulation of key oncogenic pathways. Increasing evidence of the link between MSI and miRNAs in LS prompted a deeper investigation into the miRNome involved in these diseases. In this regard, in this study, we discuss the emerging role of miRNAs as crucial players in the onset and progression of LS as well as their potential use as disease biomarkers and therapeutic targets in the current view of precision medicine.